The long term goal of this application by the Ontario Familial Breast Cancer Registry (OFR) is to participate as part of the Breast Cancer Family Registry (BCFR) to establish and maintain a hypothesis-driven research infrastructure capable of: - providing an infrastructure for a broad research agenda in the genetic epidemiology of breast and related cancers that can support a wide spectrum of interdisciplinary and translational projects - identifying and following up a cohort of individuals who span the whole spectrum of breast cancer risk and their families - identifying diverse genetically susceptible populations that could benefit from enrollment in the| preventive and therapeutic interventions - developing an adaptive and evolutionary informatics model to support the BCFR's evolving needs and facilitate cooperative research. Our specific aims are: a) to continue to maintain and enhance the BCFR, b) to expand families, and c) to take advantage of these resources to address important questions in familial and non-familial breast cancer. To carry out our research agenda as well as to maintain and further enhance the value of the BCFR for our use and that of other investigators, we propose the following core infrastructure components and platforms: 1) follow-up, 2) targeted recruitment and expansion of populations of special interest, 3) clinical, 4) pathology, 5) biospecimens, 6) molecular, 7) analytic/informatics, 8) behavioral/survivorship and 9) administration, travel, and coordination. The OFR proposes a collaborative research agenda to focus on four themes: 1) identification of genetic factors related to breast cancer risk, 2) investigation of environmental modifiers of breast cancer risk, 3) translational and clinical studies and 4) behavioral response to familial breast cancer. The themes form a bi-directional continuum of research from basic biology to clinical practice to address our overriding goal of understanding the causes of breast cancer, developing new strategies for primary prevention, and developing new approaches that will impact on patient care.